PMID- 19821764
OWN - NLM
STAT- MEDLINE
DCOM- 20100708
LR  - 20131121
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Linking)
VI  - 25
IP  - 1
DP  - 2010 Jan
TI  - Ferritin ferroxidase activity: a potent inhibitor of osteogenesis.
PG  - 164-72
LID - 10.1359/jbmr.091002 [doi]
AB  - Hemochromatosis is a known cause of osteoporosis, and iron overload has 
      deleterious effects on bone. Although iron overload and its association with 
      osteoporosis has long been recognized, the pathogenesis and exact role of iron 
      have been undefined. Bone is an active tissue with constant remodeling capacity. 
      Osteoblast (OB) development and maturation are under the influence of core 
      binding factor alpha-1 (CBF-alpha1), which induces expression of OB-specific 
      genes, including alkaline phosphatase, an important enzyme in early osteogenesis, 
      and osteocalcin, a noncollagenous protein deposited within the osteoid. This 
      study investigates the mechanism by which iron inhibits human OB activity, which 
      in vivo may lead to decreased mineralization, osteopenia, and osteoporosis. We 
      demonstrate that iron-provoked inhibition of OB activity is mediated by ferritin 
      and its ferroxidase activity. We confirm this notion by using purified ferritin 
      H-chain and ceruloplasmin, both known to possess ferroxidase activity that 
      inhibited calcification, whereas a site-directed mutant of ferritin H-chain 
      lacking ferroxidase activity failed to provide any inhibition. Furthermore, we 
      are reporting that such suppression is not restricted to inhibition of 
      calcification, but OB-specific genes such as alkaline phosphatase, osteocalcin, 
      and CBF-alpha1 are all downregulated by ferritin in a dose-responsive manner. 
      This study corroborates that iron decreases mineralization and demonstrates that 
      this suppression is provided by iron-induced upregulation of ferritin. In 
      addition, we conclude that inhibition of OB activity, mineralization, and 
      specific gene expression is attributed to the ferroxidase activity of ferritin.
CI  - 2010 American Society for Bone and Mineral Research
FAU - Zarjou, Abolfazl
AU  - Zarjou A
AD  - Department of Medicine, University of Debrecen, 4012 Debrecen, Hungary.
FAU - Jeney, Viktoria
AU  - Jeney V
FAU - Arosio, Paolo
AU  - Arosio P
FAU - Poli, Maura
AU  - Poli M
FAU - Zavaczki, Erzsebet
AU  - Zavaczki E
FAU - Balla, Gyorgy
AU  - Balla G
FAU - Balla, Jozsef
AU  - Balla J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - 0 (Core Binding Factor Alpha 1 Subunit)
RN  - 0 (Phosphates)
RN  - 104982-03-8 (Osteocalcin)
RN  - 9007-73-2 (Ferritins)
RN  - 9013-31-4 (Apoferritins)
RN  - E1UOL152H7 (Iron)
RN  - EC 1.16.3.1 (Ceruloplasmin)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
MH  - Alkaline Phosphatase/metabolism
MH  - Apoferritins/metabolism
MH  - Calcification, Physiologic/drug effects
MH  - Cell Line
MH  - Ceruloplasmin/*metabolism/pharmacology
MH  - Core Binding Factor Alpha 1 Subunit/metabolism
MH  - Down-Regulation/drug effects
MH  - Ferritins/*metabolism/pharmacology
MH  - Humans
MH  - Intracellular Space/drug effects/metabolism
MH  - Iron/pharmacology
MH  - Organ Specificity/drug effects
MH  - Osteoblasts/metabolism
MH  - Osteocalcin/metabolism
MH  - *Osteogenesis/drug effects
MH  - Phosphates/metabolism
EDAT- 2009/10/14 06:00
MHDA- 2010/07/09 06:00
CRDT- 2009/10/14 06:00
PHST- 2009/10/14 06:00 [entrez]
PHST- 2009/10/14 06:00 [pubmed]
PHST- 2010/07/09 06:00 [medline]
AID - 10.1359/jbmr.091002 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2010 Jan;25(1):164-72. doi: 10.1359/jbmr.091002.